外源性瘦素对硫代乙酰胺致急性肝损伤保护机制的研究  

Study on protection mechanism of exogenous leptin against thioactitmide-induced acute liver injury

作　　者：黄国荣[1] 丁忠阳[1] 张家明[1] 

机构地区：[1]南京医科大学附属无锡市人民医院,江苏无锡214023

出　　处：《中国医药导报》2012年第35期20-21,共2页China Medical Herald

基　　金：南京医科大学科技发展基金面上项目(项目编号:2010NJ-MU096)

摘　　要：目的探讨外源性瘦素在硫代乙酰胺(Thioactitmide,TAA)所致急性肝损伤早期保护中的作用及可能机制。方法 36只雄性Wistar大鼠分为正常组、TAA造模组及外源性瘦素预处理组,每组12只。外源性瘦素预处理组于建立急性肝损伤模型前1 h腹腔内注射200 mg/kg外源性瘦素。三组大鼠分别于造模后24 h处死。测定各组小鼠血浆丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肿瘤坏死因子α(TNF-α)水平,采用RT-PCR法测定各组小鼠肝组织TNF-α,核因子-κB(nuclear factor kappa B,NF-κB)mRNA的表达情况。结果外源性瘦素预处理组ALT、AST水平较TAA造模组明显降低(P<0.01);外源性瘦素预处理组TNF-α水平较TAA造模组明显降低(P<0.01);外源性瘦素预处理组TNF-α和NF-κB mRNA表达较TAA造模组明显降低(均P<0.01)。结论外源性瘦素预处理在TAA所致急性肝损伤中可通过抑制肝脏NF-κB活化,进而抑制TNF-α表达,减轻肝损伤,发挥保护作用。Objective To investigate the protective effect of exogenous leptin against thioactitmide（TAA）-induced acute liver injury and the possible mechanism.Methods 36 male Wistar rats were randomly divided into the normal group,TAA model group and exogenous leptin pretreatment group,of 12 rats each group.The rats in the exogenous leptin pretreatment group were intraperitoneally injected with 200 mg/kg exogenous leptin 1 hour prior to establishment of acute liver injury model.All rats were sacrificed 24 h after establishment of the model.The serum levels of ALT,AST and tumor necrosis factor α（TNF-α） were detected,and the mRNA expression of TNF-α and nuclear factor kappa B（NF-κB） in hepatic tissues was determined using RT-PCR assay.Results The serum concentrations of ALT and AST in the exogenous leptin pretreatment group were significantly higher than those in the normal group（P 0.01）,the serum TNF-α concentration in the exogenous leptin pretreatment group was significantly higher than that in the normal group（P 0.01）,and the mRNA expression of NF-κB and TNF-α in the exogenous leptin pretreatment group were significantly higher than that in the normal group（all P 0.01）.Conclusion Exogenous leptin alleviates TAA-induced acute liver injury and exhibits protection through inhibiting NF-κB activation and suppressing TNF-α expression.

关 键 词：急性肝损伤 硫代乙酰胺 外源性瘦素 保护机制 

分 类 号：R575.3[医药卫生—消化系统]